title: Knockdown of FABP3 impairs cardiac development in Zebraﬁsh through the retinoic acid signaling pathway.
abstract: Fatty acid-binding protein 3 (FABP3) is a member of the intracellular lipid-binding protein family, and is primarily expressed in cardiac muscle tissue. Previously, we found that FABP3 is highly expressed in patients with ventricular-septal defects and is often used as a plasma biomarker in idiopathic dilated cardiomyopathy, and may play a significant role in the development of these defects in humans. In the present study, we aimed to investigate the role of FABP3 in the embryonic development of the zebrafish heart, and specifically how morpholino (MO) mediated knockdown of FABP3 would affect heart development in this species. Our results revealed that knockdown of FABP3 caused significant impairment of cardiac development observed, including developmental delay, pericardial edema, a linear heart tube phenotype, incomplete cardiac loop formation, abnormal positioning of the ventricles and atria, downregulated expression of cardiac-specific markers and decreased heart rate. Mechanistically, our data showed that the retinoic acid (RA) catabolizing enzyme Cyp26a1 was upregulated in FABP3-MO zebrafish, as indicated by in situ hybridization and real-time PCR. On the other hand, the expression level of the RA synthesizing enzyme Raldh2 did not significantly change in FABP3-MO injected zebrafish. Collectively, our results indicated that FABP3 knockdown had significant effects on cardiac development, and that dysregulated RA signaling was one of the mechanisms underlying this effect. As a result, these studies identify FABP3 as a candidate gene underlying the etiology of congenital heart defects.
authors.affiliation: Department of Emergency, Subei People Hospital, Yangzhou, Jiangsu 225001, China. chunmeishi@njmu.edu.cn.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Wang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Guixian
authors.initials: G
authors.lastname: Song
authors.forename: Yahui
authors.initials: Y
authors.lastname: Shen
authors.forename: Hailang
authors.initials: H
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Shi
authors.forename: Lingmei
authors.initials: L
authors.lastname: Qian
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics; D006801:Humans; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C476998:Fabp3 protein, zebrafish; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D029961:Zebrafish Proteins; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; C000607085:cyp26a1 protein, zebrafish; C518907:Aldh1a2 protein, zebrafish; D050697:Retinal Dehydrogenase